Intravenous Infusion of Human Mesenchymal Stem Cells (HMM910 ) in Postmenopausal Women With Osteoporosis at High Risk of Fracture

Inclusion criteria

All of the following criteria must be met for inclusion:

• Willingness to participate in the clinical trial and signing of informed consent;
• Female, age between 45 (inclusive) and 85 (inclusive) years, with primary menopause for ≥2 years;
• Body weight ≥40 kg, and body mass index (BMI) between 18 kg/m² (inclusive) and 30 kg/m² (inclusive);
• Those who meet the diagnostic criteria for osteoporosis and have one of the following conditions: ① Fragile fracture occurred in the past 2 years; ② Suffered a fracture while receiving anti-osteoporosis medication; ③ History of multiple-site fractures (including vertebral, hip, proximal humerus, or distal radius, etc.); ④ Bone mineral density (BMD) T-score < -3.0 at the lumbar spine (L1-L4) or hip (total hip or femoral neck) as measured by DXA; ⑤ High risk of falling; ⑥ Calculated by FRAX (Fracture Risk Assessment Tool), a 10-year risk of major osteoporotic fracture >30% or hip fracture risk >4.5%; ⑦ Currently using medications known to cause skeletal harm [such as high-dose glucocorticoids (prednisolone ≥7.5 mg/day for over 3 months), etc.].

Exclusion criteria

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Subjects who meet one or more of the following criteria will be excluded:

• Diseases affecting bone metabolism: various metabolic bone diseases such as osteogenesis imperfecta and osteomalacia; Paget's disease of bone, hypercalcemia, hypocalcemia (participants must not have used calcium supplements within 24 hours before blood sampling for serum calcium screening); Cushing's syndrome, hyperprolactinemia; hypopituitarism; acromegaly, etc.; hyperparathyroidism or hypoparathyroidism; secondary menopause, etc.
• Secondary osteoporosis and other severe conditions, such as primary bone tumors (e.g., multiple myeloma, osteosarcoma, chondrosarcoma), secondary bone tumors, hematologic malignancies, or drug-induced osteoporosis.
• Current malignancy, history of malignancy not cured for at least 5 years, or disability due to severe or long-term diseases (such as stroke, Parkinson's disease, multiple sclerosis) resulting in inability to ambulate.
• Severe infectious diseases, autoimmune diseases (e.g., systemic lupus erythematosus), uncontrolled severe hypertension, or diabetes mellitus with severe complications or unstable blood glucose; severe cardiovascular, cerebrovascular, or other significant diseases.
• Allergic constitution: known allergy to products derived from mammalian cells or to the investigational product of clinical significance.
• Patients who have undergone major organ or bone marrow transplantation; patients who have received external radiation or skeletal implantation of radioactive materials.
• Patients who have previously received any form of cell therapy.
• Previous treatment with anti-osteoporosis drugs or medications affecting bone metabolism: ① Treatment with any PTH analog within the past 6 months (including participation in clinical trials of similar products); ② Treatment with any RANKL inhibitor (such as denosumab) within the past year; ③ Cumulative use of oral bisphosphonates for ≥3 years; or cumulative use >3 months but <3 years with the last dose administered within 6 months before screening, or intravenous bisphosphonate use within 24 months before screening.
• DXA measurement: ① Fewer than two lumbar vertebrae were measurable by DXA; ② Height, weight, or body size may impede accurate DXA measurement.
• HBV-DNA ≥1,000 copies (cps)/mL or above the upper limit of normal; hepatitis C virus (HCV) antibody positive and HCV RNA copies above the upper limit of normal; positive syphilis antibody, or HIV antibody.
• Malabsorption syndromes, such as Crohn's disease and chronic pancreatitis. Known impaired absorption of calcium or vitamin D.
• History of neurological or psychiatric disorders.
• Current uncontrolled thyroid disease, hyperthyroidism, or hypothyroidism; thyroid stimulating hormone (TSH) level below normal range; TSH elevated (>5.5 μIU/mL but ≤10.0 μIU/mL) and serum T4 outside the normal range; TSH >10.0 μIU/mL.
• Known severe hepatic insufficiency (AST or ALT ≥2×ULN, ALP or total bilirubin ≥1.5×ULN), liver cirrhosis, unstable liver disease, or known clinically significant biliary anomalies as judged by the investigator (excluding Gilbert's syndrome or asymptomatic gallstones); known moderate to severe chronic kidney disease (eGFR <60 mL/min/1.73 m²).
• Evidence of alcohol abuse or drug abuse within 12 months before screening, as determined by the investigator, may interfere with the understanding or completion of the study by the participant.
• Participation in another clinical trial within 6 months before screening.
• Other conditions deemed by the investigator as unsuitable for participation.